The invention relates to a nuclear magnetic resonance device (hereinafter referred to as xe2x80x9cNMR devicexe2x80x9d) wherein a sample supply source and the NMR device are connected through a flow path, so that a sample supplied from the sample supply source can be analyzed on-line. For example, the present invention is applied to a case such that a liquid chromatograph (hereinafter referred to xe2x80x9cLCxe2x80x9d) device and the NMR device are connected through the flow path, and the sample taken out of the LC device is sequentially sent to the NMR device to carry out a measurement.
In the NMR measurement, there has been widely used an off-line measurement wherein the sample is collected to respective sampling tubes with bottoms by using a heavy water type (heavy alcohol-type) solvent necessary for the measurement, and the respective sampling tubes are separately attached to an NMR probe, i.e. measuring probe, positioned in a measuring space of the NMR device to carry out the NMR measurement. However, recently, in order to automate the measurement, there has been also used an NMR device of an on-line measurement to send the sample through a flow path directly from the sample supply source without using the sampling tubes with the bottoms.
FIG. 3 is a block diagram showing a conventional liquid chromatograph-nuclear magnetic resonance system (hereinafter referred to as xe2x80x9cLC-NMR systemxe2x80x9d) wherein the LC device and NMR are connected on line. The system includes an LC portion and an NMR device.
In the LC portion, a mobile phase 1 is sent to a flow path by a liquid sending pump 2, and a sample is introduced from a sample introducing portion 3 disposed on a middle way of the flow path. The introduced sample is subjected to component separation at a column 4, and every component is sequentially sent through the column 4. The movable phase 1 is prepared by controlling concentrations of a heavy water-type solvent which has a high ability for allowing the column to absorb the sample, and a heavy alcohol-type solvent which has a low ability for allowing the column to absorb the sample. Incidentally, the reason why a light water-type solvent and a light alcohol-type solvent are not used is that in case an NMR measurement, described later, is carried out, it is necessary to use the heavy water-type/heavy alcohol-type solvents instead of the light water-type/light alcohol-type solvents. Then, the sample components passing through the column 4 are detected by a detector 5 for carrying out the measurements by an electric conductivity and UV.
The NMR device is structured such that a measuring space is provided in a ferromagnetic field space formed of electromagnets, and an electromagnetic wave necessary for the NMR measurement is generated in the measuring space by a device control portion. Also, an NMR coil 20 for receiving and sending the measured electromagnetic wave signal is attached thereto.
A sample flow path 21 is connected to the latter step of the detector 5 of the LC portion so that the flow path 21 passes through the NMR coil 20 in the axial direction. Then, a capacity of the pipe from the detector 5 to the NMR coil 20 is measured in advance and a liquid transfer speed, i.e. liquid transfer quantity per unit hour, of the mobile phase can be obtained from the rotation number of the pump, so that a time from a moment when the sample to be measured is detected at the detector 5 to a moment when the sample to be measured arrives at the NMR coil position, can be calculated.
Therefore, when the detector 5 detects the sample to be measured, a time when the sample to be measured arrives at the NMR coil position is calculated based on a pipe capacity and a liquid transfer speed and the liquid transfer of the mobile phase is stopped immediately after the arriving time elapses, so that the sample can be retained in the NMR coil position. Thus, the NMR measurement of the substances present in the sample flow path area at the NMR coil position can be carried out. Or, even if the liquid transfer is not stopped, when the measurement is started corresponding to the time when the sample passes through the NMR coil position, the NMR measurement of the sample to be measured can be done.
Thus, since the NMR measurement can be carried out only at the portion passing through the NMR coil 20 out of the entire sample flow path 21, an NMR probe 22 for the measurement is substantially formed by the NMR coil 20 and the part of the sample flow path 21 passing through the NMR coil 20. Incidentally, the end portion of the sample flow path 21 is connected to a drain to thereby abandon the sample after measurement.
FIG. 4 is an enlarged drawing of the NMR probe portion in FIG. 3. The NMR coil 20 is wound around a cylindrical tube 23. The sample flow path 21 passes through the tube 23.
As described above, in the conventional NMR probe 22, the hollow sample flow path 21 passes through the NMR coil 20 as it is. In case the sample is measured in the device, there is employed either a method wherein when the sample is sent, the sample is measured within the time while the sample flows in the NMR probe 22, i.e. on-flow measurement, or a method wherein when the sample is sent, the liquid transfer pump 9 is stopped to temporarily stop flow of the sample so that the sample is retained in the NMR probe 22 to extend an integrating time and measure, i.e. stopped-flow measurement.
However, in case the on-flow measurement is carried out, for example, there may be a case wherein when a flow speed of the sample is fast, a sufficient measuring time can not be taken and a proper integrating process can not be done, which results in a measurement with a lower S/N ratio. On the other hand, in case of the stopped-flow measurement, since the sample is inevitably dispersed in the back-and-forth direction in the flow path during the suspension, for example, there may be a case wherein only the sample in the order of 30% of the entire quantity remains in the vicinity of the NMR coil. Even if the integrating time is extended through the integrating process, the sufficient S/N ratio can not be obtained due to dilution of the sample dispersion as a whole. Also, due to the dispersion of the sample, a quantitative measurement may not be carried out.
Also, when the sample to be measured arrives at the position of the NMR coil 20, the NMR measurement is carried out. However, it is very difficult to accurately determine the timing. For the sake of safety, the sample is normally sent in a slightly dispersed state so that a flow path length where the sample to be measured is present becomes longer when compared with the length of the sample flow path in the NMR coil. Thus, even if the timing is slightly shifted, it has to be practiced that the sample is present in the position of the NMR coil. Therefore, the quantity of the sample actually contributing to the measurement is only a part out of the whole measuring sample sent from the sample supply source, so that there has been a limit for raising the S/N ratio.
Further, the expensive heavy water/heavy alcohol-type solvents have to be used at the time of the NMR measurement. However, such an expensive solvent should be used as little as possible. In other words, if possible, light water/light alcohol-type solvents should be used as much as possible. Especially, since the heavy alcohol-type solvent is extremely expensive, it is desirable to reduce its using quantity. In a system wherein the LC portion is connected in the preceding step of the NMR device as described above, since the separation column is provided, it is necessary to use a mixture wherein the heavy alcohol type-solvent is mixed in the mobile phase (because it is difficult to allow the sample to pass through a long column by only the heavy water-type solvent), a large quantity of the expensive heavy alcohol is required.
Furthermore, while it is necessary to keep the sample at a high concentration as much as possible during the NMR measurement, after completion of the measurement, it is desirable to discharge the sample from the NMR probe position as quickly and effectively as possible.
In view of the above problems, the present invention has been made and an object of the invention is to provide an NMR device, wherein a measurement with a high sensitivity and S/N ratio can be made by effectively using a very small quantity of sample.
Another object of the invention is to provide an NMR device as stated above, wherein a flowing sample can be easily and accurately held at a measuring position.
A further object of the invention is to provide an NMR device as stated above, wherein an expensive solvent to be used at the NMR measurement can be reduced as little as possible.
A still further object of the invention is to provide an NMR device as stated above, wherein the sample can be extremely concentrated when it is required to retain the sample in the NMR probe for measurement, and when it is required to discharge the sample from the NMR probe after the measurement, the sample can be discharged quickly and effectively.
A still further object of the invention is to provide an NMR device as stated above, wherein when an on-flow measurement is carried out, it is possible to control a time for retaining the sample in the NMR probe.
Further objects and advantages of the invention will be apparent from the following description of the invention.
In order to attain the above objects, according to a first aspect of the invention, an NMR device includes an NMR coil for receiving and sending an electromagnetic wave in a measuring space of the NMR device, and a sample flow path connected from a sample supply source and passing through the NMR coil. In the NMR device wherein a portion passing through the NMR coil out of the whole sample flow path functions as an NMR probe to thereby carry out an on-line measurement, a filler for absorbing the sample in the sample flow path of the NMR probe position is provided.
According to a second aspect of the invention, an NMR device includes an NMR coil for receiving and sending an electromagnetic wave provided in a measuring space of the NMR device, and a sample flow path connected to the sample supply source and passing through the NMR coil. In the NMR device wherein only a portion passing through the NMR coil out of the whole sample flow path functions as an NMR probe to thereby carry out an on-line measurement, a filler for absorbing the sample is provided in the sample flow path of the NMR probe. Also, a sample supply flow path connected to the sample supply source of the sample flow path provided on an upper stream side than the NMR probe and a solvent flow path for substituting a solvent are connected to be switched over by a switching device.
According to a third aspect of the invention, an NMR device includes an NMR coil for receiving and sending an electromagnetic wave provided in a measuring space of the NMR device, and a sample flow path connected to pass through the NMR coil from a sample supply source. In the NMR device wherein only a portion passing through the NMR coil out of the whole sample flow path functions as an NMR probe to thereby carry out an on-line measurement, a filler for absorbing the sample is provided in the sample flow path of the NMR probe. Also, a sample supply flow path connected to the sample supply source of the sample flow path provided on an upper stream side than the NMR probe and a solvent flow path for selectively substituting from more than two solvents or a mixture thereof, are connected to be switched over by a switching device.
According to the first aspect of the invention, since the filler for absorbing the sample is provided in the sample flow path passing through the NMR probe portion, the sample flowing through the flow path is positively caught by the filler in the NMR probe. By selecting the kinds of the filler and the solvent, the retained time of the sample can be controlled. Thus, by selecting the filler and the solvent according to the sample, a sufficient integrating time necessary for the measurement can be obtained. Also, since the sample itself is caught by the filler, the sample is concentrated and not dispersed in the sample flow path. Thus, even if a measurement is carried out with a very small quantity of the sample, there are no problems such that an S/N ratio is reduced, and a quantitative measurement is impossible.
According to the second aspect, the cheap light water/light alcohol-type solvents are used while the sample flows from the sample supply source to the switching device, and the heavy water/heavy alcohol-type solvents are used in the sample flow path after the switching device. Thus, a quantity of the expensive heavy water/heavy alcohol-type solvents to be used can be reduced.
According to the third aspect, since an absorbing ability of the sample by a combination of the solvent and the filler supplied from the solvent flow path can be controlled, a solvent having a high absorbing ability of the sample is used during the measurement, and a solvent having a low absorbing ability of the sample is used after the measurement to thereby quickly discharge the sample. Or, in an on-flow measurement, a remaining time of the sample in the NMR probe can be controlled at will by properly mixing more than two solvents.